Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacter cloacae have been recently recognized in the United States. Whole-genome sequencing (WGS) has become a useful tool for analysis of outbreaks and for determining transmission networks of multidrug-resistant organisms in healthcare settings, including carbapenem-resistant Enterobacteriaceae (CRE). We experienced a prolonged outbreak of CRE of E. cloacae and K. pneumoniae over a three-year period at a large academic burn center despite rigorous infection control measures...

We report on a mother-to-child transmission of KPC carbapenemase-producing Klebsiella pneumoniae at birth followed by subsequent cases in the NICU. Molecular analysis of isolates showed production of KPC-3 enzyme. The only potential risk factor identified for the mother was previous activity as a caregiver. Present findings suggest consideration of pro-active surveillance in pregnant women with risk factors for colonization.

K. pneumoniae isolates carrying blaKPC-3 gene were collected to perform Bayesian phylogenetic and selective pressure analysis and to apply homology modeling to the KPC-3 protein. A dataset of 44 blakpc-3 gene sequences from clinical isolates of K. pneumoniae was used for Bayesian phylogenetic, selective pressure analysis and homology modeling. The mean evolutionary rate for blakpc-3 gene was 2.67×10(-3) substitution/site/year (95% HPD: 3.4×10(-4-)5.59×10(-)(3)). The root of the Bayesian tree dated back to the year 2011 (95% HPD: 2007-2012)...

To date, only a few sporadic cases of infections due to Klebsiella pneumoniae carbapenemase (KPC) producers have been reported in Portugal. Here, we report for the first time an outbreak of K. pneumoniae KPC-3 producers in a tertiary-care hospital during 2013. Twenty-seven ertapenem-resistant K. pneumoniae were identified in patients at a tertiary-care hospital during 2013 isolated predominantly from urine (48·1%) and blood (25·9%) cultures. All isolates were highly resistant to β-lactam antibiotics and most showed intermediate resistance to imipenem...

OBJECTIVE: We describe the characterization of a new isolated in Spain of Klebsiella pneumoniae ST258 producing KPC-3, carbapenems non-susceptible, recovered from a sample of urine from a patient with urinary tract infection and no history of carbapenems exposure. METHODS: After the isolation, identification of K. pneumoniae was performed by biochemical tests and mass spectrometry. The carbapenems susceptibility testing was performed by microdilution and E-test in cation-adjusted Mueller-Hinton...

OBJECTIVES: The spread of carbapenem-resistant Enterobacteriaceae (CRE) represents one of the most worrisome problems for clinical medicine worldwide. In Italy, the Antibiotic-Resistance-Istituto Superiore di Sanità surveillance network, in collaboration with the Committee for Antimicrobial Agents of the Italian Society of Clinical Microbiologists, promoted a study to investigate the carbapenem-resistance mechanisms, clonal relatedness and capsular typing of a recent collection of carbapenem-resistant Klebsiella pneumoniae (CR-KP)...

Carbapenem resistance in Klebsiella pneumoniae is important because of its increasing prevalence and limited therapeutic options. To investigate the clinical and microbiological characteristics of patients infected or colonized with carbapenem non-susceptible K. pneumoniae (CnsKP) in Taiwan, we conducted a retrospective study at Taipei Veterans General Hospital from January 2012 to November 2013. Carbapenem non-susceptibility was defined as a minimum inhibitory concentration (MIC) of ≥2 mg/L for imipenem or meropenem...

OBJECTIVES: We analysed the microbiological traits and population structure of KPC-producing Enterobacteriaceae isolates collected in Spain between 2012 and 2014. We also performed a comparative WGS analysis of the three major KPC-producing Klebsiella pneumoniae clones detected. METHODS: Carbapenemase and ESBL genes were sequenced. The Institut Pasteur MLST scheme was used. WGS data were used to construct phylogenetic trees, to identify the determinants of resistance and to de novo assemble the genome of one representative isolate of each of the three major K...

INTRODUCTION: An analysis was made about the evolution of resistance to 3rd generation cephalosporins, imipenem, and other antibiotics in invasive isolates of Klebsiella pneumoniae (K. pneumoniae) according to the Spanish EARS-Net database (2010-2014). METHODS: Forty-two hospitals from 16 Autonomous Communities with an approximate population coverage of 33% participated. RESULTS: A total 7,140 pneumoniae corresponding to the same number of patients were studied...

KPC-3-producing bacteria are endemic in many countries but only recently became apparent their wide distribution in different Portuguese hospitals. The aim of this study is to characterize genetic backgrounds associated with bla KPC-3 among Klebsiella pneumoniae isolates recently identified on non-hospitalized patients in Portugal. Twenty KPC-producing K. pneumoniae identified between October 2014 and November 2015 in three different community laboratories were characterized. Isolates were mainly from patients from long-term care facilities (n = 11) or nursing homes (n = 6), most of them (75%) previously hospitalized in different Portuguese hospitals...

A novel mcr variant, named mcr-1.2, encoding a Gln3-to-Leu functional variant of MCR-1, was detected in a KPC-3-producing ST512 Klebsiella pneumoniae isolate collected in Italy from a surveillance rectal swab from a leukemic child. The mcr-1.2 gene was carried on a transferable IncX4 plasmid whose structure was very similar to that of mcr-1-bearing plasmids previously found in Escherichia coli and K. pneumoniae strains from geographically distant sites (Estonia, China, and South Africa).

Eravacycline is a novel, fully synthetic fluorocycline antibiotic of the tetracycline class being developed for the treatment of complicated urinary tract infections and complicated intra-abdominal infections. Eravacycline has activity against many key Gram-negative pathogens, including Enterobacteriaceae resistant to carbapenems, cephalosporins, fluoroquinolones and β-lactam/β-lactamase inhibitor combinations, including strains that are multidrug-resistant. Carbapenem-resistant Enterobacteriaceae (CRE) isolates from 2010 to 2013 (n=110) were characterized for carbapenemase genes by PCR and sequencing...

We describe the interspecies transmission of the plasmid-mediated blaKPC-3 gene, which confers carbapenem resistance, between clinically relevant gram-negative bacteria in a single patient. A KPC-3 producing Enterobacter aerogenes was isolated from a hospitalized patient previously colonized and then infected by a Klebsiella pneumoniae ST101 carrying the blaKPC-3 gene. The strains showed identical plasmids. Since intense horizontal exchanges among bacteria can occur in the gut, clinicians should be aware that patients colonized by carbapenem-resistant K...

The Klebsiella pneumoniae carbapenemase (KPC), first described in the United States in 1996, is now a widespread global problem in several Gram-negative species. A worldwide surveillance study collected Gram-negative pathogens from 202 global sites in 40 countries during 2012 to 2014 and determined susceptibility to β-lactams and other class agents by broth microdilution testing. Molecular mechanisms of β-lactam resistance among carbapenem-nonsusceptible Enterobacteriaceae and Pseudomonas aeruginosa were determined using PCR and sequencing...

To better understand the antibacterial activity of S-649266 against carbapenemase producers, its stability against clinically relevant carbapenemases was investigated. The catalytic efficiencies (kcat/Km) of IMP-1, VIM-2, and L1 for S-649266 were 0.0048, 0.0050, and 0.024 μM(-1) s(-1), respectively, which were more than 260-fold lower than that for meropenem. Only slight hydrolysis of S-649266 against KPC-3 was observed. NDM-1 hydrolyzed meropenem 3-fold faster than S-649266 at 200 μM.

Klebsiella pneumoniaesequence type (ST) 307, carryingblaKPC-3,blaCTX-M-15,blaOXA-1,aac(6')-Ib-cr, andqnrB1 genes, is replacing the predominant hyperepidemic ST258 clone in Italy. Whole-genome and complete plasmid sequencing of one ST307 strain was performed and new features were identified.

OBJECTIVES: Temocillin is a 6-α-methoxy derivative of ticarcillin that shows in vitro activity against Enterobacteriaceae producing Klebsiella pneumoniae carbapenemase (KPC). Our objective was to assess in vivo temocillin activity against KPC-producing Escherichia coli. METHODS: Isogenic derivatives of the WT E. coli CFT073 producing KPC-2, KPC-3 or OXA-48 were constructed. An experimental murine model of intra-abdominal infection with sepsis was used. Mice were treated subcutaneously with temocillin 200 mg/kg every 2 h for 24 h, reproducing the duration of time that the free serum concentration of temocillin exceeded the MIC in humans with a regimen of 2 g every 12 h or 2 g every 8 h...

The usefulness of β-lactam antimicrobial agents is threatened as never before by β-lactamase-producing bacteria. For this reason, there has been renewed interest in the development of broad-spectrum β-lactamase inhibitors. Herein we describe the results of dose fractionation and dose-ranging studies carried out using a one-compartment in vitro infection model to determine the exposure measure for CB-618, a novel β-lactamase inhibitor, most predictive of the efficacy when given in combination with meropenem...

INTRODUCTION: Resistance to carbapenems is considered to represent a serious threat to public health at the global level, since these antibiotics are one of the last therapeutic options for the treatment of multidrug-resistant bacteria. Molecular characterization of outbreaks due to resistant bacteria provides information that can be used in the design of infection control strategies. OBJECTIVE: To describe the molecular characteristics of an outbreak of carbapenem-resistant Klebsiella pneumoniae that occurred in a tertiary care hospital in Medellín in 2010-2011...